Biosynthesis and metabolism of endocannabinoids and their congeners from the monoacylglycerol and N-acyl-ethanolamine families

Simard, Marie; Archambault, Anne-Sophie; Lavoie, Jean-Philippe C.; Dumais, Élizabeth; Marzo, Vincenzo Di; Flamand, Nicolas

doi:10.1016/j.bcp.2022.115261

Cited by 25 publications

(26 citation statements)

References 139 publications

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“…30−32 The N-arachidonoyl-ethanolamine, anandamide (AEA), is an endocannabinoid implicated in numerous physiological processes, such as cognition, inflammatory pain, and inflammation. 30 AEA is released by hydrolysis of Narachidonoyl-substituted phosphatidylethanolamine species generated from the transfer of arachidonic acid to phosphatidylethanolamine (PE). A previous study has reported that the levels of anandamide are lowered in the midfrontal cortex and temporal cortex of AD patients compared to controls.…”

Section: ■ Discussionmentioning

confidence: 99%

“…The metabolic pathways retrieved based on the KEGG database and from the literature were used to plot and summarize the perturbed key metabolic pathways for AD in Figure . − The N-arachidonoyl-ethanolamine, anandamide (AEA), is an endocannabinoid implicated in numerous physiological processes, such as cognition, inflammatory pain, and inflammation . AEA is released by hydrolysis of N-arachidonoyl-substituted phosphatidylethanolamine species generated from the transfer of arachidonic acid to phosphatidylethanolamine (PE).…”

Section: Discussionmentioning

confidence: 99%

“…The fatty acid amide hydrolase-1 (FAHH-1) was performed to degrade AEA into arachidonic acid (AA) and ethanolamine, so the metabolites of AA metabolism were characterized by targeted analysis . In this study, leukotriene B4 (LTB4), leukotriene A4 (LTA4), leukotriene E4 (LTE4), prostaglandin H2 (PGH 2 ), prostaglandin F2α (PGF2α), 20-HETE, and 11,12-DHET were identified by either targeted or untargeted metabolomic analysis.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of Hair Metabolome in 5xFAD Mice and Patients with Alzheimer’s Disease Using Mass Spectrometry-Based Metabolomics

Chang,

Hsu,

et al. 2024

ACS Chem. Neurosci.

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Hair emerged as a biospecimen for long-term investigation of endogenous metabolic perturbations, reflecting the chemical composition circulating in the blood over the past months. Despite its potential, the use of human hair for metabolomics in Alzheimer's disease (AD) research remains limited. Here, we performed both untargeted and targeted metabolomic approaches to profile the key metabolic pathways in the hair of 5xFAD mice, a widely used AD mouse model. Furthermore, we applied the discovered metabolites to human subjects. Hair samples were collected from 6-month-old 5xFAD mice, a stage marked by widespread accumulation of amyloid plaques in the brain, followed by sample preparation and high-resolution mass spectrometry analysis. Forty-five discriminatory metabolites were discovered in the hair of 6-month-old 5xFAD mice compared to wild-type control mice. Enrichment analysis revealed three key metabolic pathways: arachidonic acid metabolism, sphingolipid metabolism, and alanine, aspartate, and glutamate metabolism. Among these pathways, six metabolites demonstrated significant differences in the hair of 2month-old 5xFAD mice, a stage prior to the onset of amyloid plaque deposition. These findings suggest their potential involvement in the early stages of AD pathogenesis. When evaluating 45 discriminatory metabolites for distinguishing patients with AD from nondemented controls, a combination of L-valine and arachidonic acid significantly differentiated these two groups, achieving a 0.88 area under the curve. Taken together, these findings highlight the potential of hair metabolomics in identifying disease-specific metabolic alterations and developing biomarkers for improving disease detection and monitoring.

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Section: ■ Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Characterization of Hair Metabolome in 5xFAD Mice and Patients with Alzheimer’s Disease Using Mass Spectrometry-Based Metabolomics

Chang,

Hsu,

et al. 2024

ACS Chem. Neurosci.

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“… 20 , 21 AEA is classically hydrolyzed from N-acyl-phosphatidylethanolamine by specific phospholipase D and arachidonic acid and ethanolamine by fatty acid amid hydrolase. 22 Arachidonic acid can be metabolized into PG that mostly acts as important mediators of inflammatory response and pain. 23 , 24 The analgesic effect of AEA in the central nervous system is tightly associated with the cannabinoid receptor 1 (CBR1), which is widely expressed at presynaptic neurons in the cerebral cortex.…”

Section: Discussionmentioning

confidence: 99%

Alterations of endogenous pain-modulatory system of the cerebral cortex in the neuropathic pain

Chen¹,

Wang²,

Gong³

et al. 2023

iScience

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“…The endocannabinoidome (eCBome), or “expanded endocannabinoid system”, includes, in addition to the cannabinoid CB1 and CB2 receptors, their ligands, anandamide ( N -arachidonoylethanoamine; AEA) and 2-arachidonoylglycerol (2-AG) and the enzymes responsible for their biosynthesis and degradation, other structurally-related lipid mediators, such as different N -acylethanolamines (NAEs) and 2-monoacylglycerols (2-MAGs), as well as lipoaminoacids, such as N -acylglycines and N -acyltaurines, and N -acylated neurotransmitters, such as N -acylserotonins [ 6 ]. Additionally, some polyunsaturated members of these families of lipids can act as substrates for lipoxygenases involved in arachidonic acid metabolism and participating in inflammation, such as 15-lipoxygenase, which, for example, can catalyse the oxidation of N -linoleyl-ethanolamine and 2-linoleoyl-glycerol to the corresponding 13-hydroxy-derivatives, 13-HODE-EA and 13-HODE-G [ 7 , 8 ]. This complex group of lipid mediators has been shown to bind G protein coupled receptor, such as GPR18, 55, 110 and 119, but also ion channels, such as TRPV1, TRPM8 and TRPA1, as well as PPARs receptors [ 9 ]; enzymes for their synthesis and degradation (in this latter case often common with NAEs or 2-MAGs) have also been described for eCBome mediators [ 7 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Altered endocannabinoidome bioactive lipid levels accompany reduced DNBS-induced colonic inflammation in germ-free mice

et al. 2023

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Background Gut microbiota are involved in the onset and development of chronic intestinal inflammation. The recently described endocannabinoidome (eCBome), a diverse and complex system of bioactive lipid mediators, has been reported to play a role in various physio-pathological processes such as inflammation, immune responses and energy metabolism. The eCBome and the gut microbiome (miBIome) are closely linked and form the eCBome - miBIome axis, which may be of special relevance to colitis. Methods Colitis was induced in conventionally raised (CR), antibiotic-treated (ABX) and germ-free (GF) mice with dinitrobenzene sulfonic acid (DNBS). Inflammation was assessed by Disease Activity Index (DAI) score, body weight change, colon weight-length ratio, myeloperoxidase (MPO) activity and cytokine gene expression. Colonic eCBome lipid mediator concentrations were measured by HPLC-MS /MS. Results GF mice showed increased levels of anti-inflammatory eCBome lipids (LEA, OEA, DHEA and 13- HODE-EA) in the healthy state and higher MPO activity. DNBS elicited reduced inflammation in GF mice, having lower colon weight/length ratios and lower expression levels of Il1b, Il6, Tnfa and neutrophil markers compared to one or both of the other DNBS-treated groups. Il10 expression was also lower and the levels of several N-acyl ethanolamines and 13-HODE-EA levels were higher in DNBS-treated GF mice than in CR and ABX mice. The levels of these eCBome lipids negatively correlated with measures of colitis and inflammation. Conclusions These results suggest that the depletion of the gut microbiota and subsequent differential development of the gut immune system in GF mice is followed by a compensatory effect on eCBome lipid mediators, which may explain, in part, the observed lower susceptibility of GF mice to develop DNBS-induced colitis.

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Biosynthesis and metabolism of endocannabinoids and their congeners from the monoacylglycerol and N-acyl-ethanolamine families

Cited by 25 publications

References 139 publications

Characterization of Hair Metabolome in 5xFAD Mice and Patients with Alzheimer’s Disease Using Mass Spectrometry-Based Metabolomics

Characterization of Hair Metabolome in 5xFAD Mice and Patients with Alzheimer’s Disease Using Mass Spectrometry-Based Metabolomics

Alterations of endogenous pain-modulatory system of the cerebral cortex in the neuropathic pain

Altered endocannabinoidome bioactive lipid levels accompany reduced DNBS-induced colonic inflammation in germ-free mice

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